Abstract
Immunotherapy is a promising approach for the treatment of cancers. Modified adenovirus 5 (Ad5) vectors have been used as a platform to deliver genes encoding tumor associated antigens (TAA). A major obstacle to Ad5 vector immunotherapy has been the induction of vector immunity following administration or the presence of pre-existing Ad5 immunity, which results in vector mitigation. It has been reported by us that the Ad5[E1-, E2b-] platform with unique deletions in the E1, E2b and E3 regions can induce potent cell mediated immunity (CMI) against delivered transgene products in the presence of pre-existing Ad5 immunity. Here we report the use of an Ad5[E1-, E2b-] vector platform expressing the TAA HER2/neu as a breast cancer immunotherapeutic agent. Ad5[E1-, E2b-]-HER2/neu induced potent CMI against HER2/neu in Ad5 naïve and Ad5 immune mice. Humoral responses were also induced and antibodies could lyse HER2/neu expressing tumor cells in the presence of complement in vitro. Ad5[E1-, E2b-]-HER2/neu prevented establishment of HER2/neu-expressing tumors and significantly inhibited progression of established tumors in Ad5 naïve and Ad5 immune murine models. These data demonstrate that in vivo delivery of Ad5[E1-, E2b-]-HER2/neu can induce anti-TAA immunity and inhibit progression of HER2/neu expressing cancers.
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Acknowledgements
This study was funded in part by NIH-NCI grant 1R43CA139663-01. We acknowledge ViraQuest Inc for amplification of the vaccines. The authors thank Dr Winston Witcomb for management and care of the animals. We also thank Carol Jones for management of the grant activities and Susan Nguyen for assistance in preparation of the paper.
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Frank R Jones work has been funded in part by the National Cancer Institutes and Etubics Corporation. All authors are employees of Etubics Corporation and are funded in part by grants from the National Cancer Institute.
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Gabitzsch, E., Xu, Y., Balcaitis, S. et al. An Ad5[E1-, E2b-]-HER2/neu vector induces immune responses and inhibits HER2/neu expressing tumor progression in Ad5 immune mice. Cancer Gene Ther 18, 326–335 (2011). https://doi.org/10.1038/cgt.2010.82
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DOI: https://doi.org/10.1038/cgt.2010.82
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